Recently, numerous reports have appeared describing the presence of liver-cell adenomas in women using oral contraceptives. Animal studies conducted at the time these agents were originally tested foretold of the possibility, but it was generally ignored. Since then, carcinogenesis has come to be viewed as a multistage process composed of two general stages, namely initiation and promotion. Evidence suggests that chronic ingestion of oral contraceptive agents may act as a promoting influence in liver. However, except for a recent report by Taper (Cancer 42, 462, 1978), these agents have not been tested using an initiation-promotion protocol. The objective of the present study is to evaluate the liver tumor promoting activity of two commonly used oral contraceptive agents, mestronol and norethylnodrel. Female Sprague Dawley derived rats are initiated by intubation of diethylnitrosamine 24 hrs. following partial hepatectomy. The animals are shifted to test diets 24 hrs. later and killed 4 and 9 months later. Preneoplstic liver lesions will be revealed by determining the number of gamma glutamyltranspeptidase foci per sq.cm. of liver. Preliminary results suggest that mestranol is a promoter of hepatocarcinogenesis. Biochemical studies on the effects of mestranol on liver are underway. The results of this entire study should shed new light on the carcinogeneic potential of oral contraceptive steroids and perhaps mechanisms of tumor production.